In the first two years of this project, we have demonstrated a significant age-related decrease in serum levels of somatomedins (SM) in Sprague-Dawley and Fischer 344 rats of both sexes. We now propose to evaluate the hypothesis that aging involves a physiologically significant deterioration in secretiton of SM by liver cells. We will study effects of age on basal and hormone-stimulated secretion of SM (and the serum protein to which this family of hormones is specifically bound) by hepatocytes isolated from male Fischer 344 rats at several ages - 6, 17, and 28 months. Our initial experiments (and two recent reports) indicate that isolated hepatocytes will be suitable for the proposed research. We propose the following sequence of experiments: 1. Completion of our current evaluation of the conditions best suited for study of SM and binding protein secretion by isolated hepatocytes. 2. Characterization of the hormone requirement for optimal secretion of SM and binding protein under these conditions. 3. Determination of the relative importance of de novo synthesis and release of preformed hormone in the secretion of SM, and of the roles of individual hormones in stimulating these processes. 4. Demonstration and localization of any age-related deficiencies in SM and binding protein secretion by liver cells from rats of the specified ages. 5. Investigation of hormone treatments which might restore SM secretion in old rats to the levels found in young and middle-aged animals. These experiments will contribute to understanding of the control, mechanism, and effects of age on somatomedin secretion by liver cells, and thus help explain the decrease with age in circulating levels of this important family of hormones.